Objectives of the overall project are (1) to elucidate the factors determining nitrogen wastage during restricted nitrogen intake in both normal subjects and patients with diseases: characterized by impaired mechanisms for waste nitrogen disposal and (2) to determine how nitrogen-free analogues of essential amino acids may be used advantageously to improve nitrogen conservation under these conditions. Specific studies include the development of an animal model for congenital hyperammonemia due to inborn errors of the urea cycle, using both genetically abnormal mice and normal growing cats; studies of components of the labile nitrogen pool in starvation, portal-systemic encephalopathy, uremia, and gyrate atrophy of the choroid and retina, and the metabolic interrelationships between these compounds development of a rational therapy for the treatment of portal-systemic encephalopathy using ornithine and arginine salts of nitrogen-free analogues of essential amino acids; studies of the mechanism of the nitrogen-sparing effect of the keto-analogue of leucine: development of optimal nutritional therapy for chronic renal insufficiency; and studies of the metabolism of nitrogen-free analogues of essential amino acids in isolated organs of normal and uremic animals.